The delivery of drugs to the skin and systemically via the skin is hampered by the natural barrier of the stratum corneum. Creams and lotions are classical vehicles for delivering drugs and cosmetics to the skin. These preparations are semi-solid, bi-phasic preparations where oil spheres are dispersed in water. The droplet size of these spheres has not been a concern in conventional pharmaceutically marketed semi-solid creams and lotions. Most commercially marketed medical creams include oil spheres having a size of 5 to 50 microns. For example, VOLTAREN EMULGEL has a droplet size above five microns, as confirmed both microscopically and with photon correlation spectroscopy (Coulter N4MD).
Moreover, the scientific literature does not address the droplet size of the internal oily phase of topically applied emulsions. On the few occasions that refer to topical cream or lotion dosage forms, the indicated droplet size is in the range of a few to tens of microns. For example, U.S. Pat. No. 4,529,601 relates to an eutectic mixture of lidocaine and tetracaine which allegedly produces a good local anesthetic effect that may not be achieved otherwise.
EP 00 63 870 claims good anti-inflammatory activity and high safety of an anti-inflammatory substance in combination with MCT oil and carboxy vinyl polymer. Again, droplet size is not emphasized.
EP 04 33 132 discloses the topical cosmetic application of vesicles for incorporation of essential oils. It is also possible, according to that patent application, that small droplets of various sizes of the essential oils may be formed.
The cases cited above exemplify numerous patents concerning topical uses of classical macroemulsions, in which the oily droplets are generally well above one micron in diameter. There is also a vast body of prior art utilizing liposome preparations for enhanced dermal penetration of pharmaceuticals (Egbaria & Weiner, Adv. Drug Delivery Rev. 5, 287 (1990)). However, there are inherent problems in formulating stable liposomes, since these structures are lipid bilayers enveloping an aqueous phase. Another type of drug carrier, distinct from both classical emulsions and liposomes are the microemulsions which are usually thermodynamically stable, transparent and have particles consistently below 200 nm (Rosano, H. L., Carallo, J. L. and Lyons, G. B. Microemulsion Systems, Vol. 24, Chap. 16, H. L. Rosano and M. Clause eds. Marcel Dekker, Inc., New York (1987), pp. 271). However, microemulsions contain a large proportion of surfactant to lipid and therefore are inappropriate for dermal applications due to anticipated problems of irritancy.
EP 05 06 197 discloses an aqueous suspension of nanoparticles of at least one lipid and an emulsifier, wherein the nanoparticles have a size of between 50 and 1000 nm. The lipids used therein, however, are either a solid lipid or a mixture of solid lipids.
In the field of topical and transdermal medication and delivery of drugs, much effort has been invested in providing chemical enhancers of drug penetration, such as DMSO and azones. Many of these substances cause irritation and are not desirable due to their toxicity. There remains a need, therefore, for a method and vehicle which will enable or facilitate efficient transport of poorly soluble drugs through the skin for topical or transdermal use, when provided as an aqueous dispersion of same.